This invention relates to the cephalosporin class of antibiotics. In particular, this invention relates to certain of such cephalosporins having in the 3-position a carboxy group or a functionality derived from said carboxy group. Such functional groups include an ester, thioester, amide, or other like groups prepared by reacting a mixed anhydride derivative or acid halide of the 3-carboxy group with the appropriate nucleophilic reagent. The compounds of this invention are therapeutically useful antibiotic compounds or intermediates useful in the preparation of such antibiotics.
Previously, numerous antibiotics of the cephalosporin class have been described. These antibiotics, all possessing the same basic ring structure comprising the 4-membered .beta.-lactam ring fused to a 6-membered dihydrothiazine ring, differ from one another structurally and biologically in many respects. Structurally, the known cephalosporin antibiotics differ in the nature of the 7-acylamido substituent and also in the nature of the substituent in the 3-position of the dihydrothiazine ring. The desacetoxycephalosporanic acids, for example, cephalexin, have a 3-methyl substituent. Numerous cephalosporins having a substituted methyl group in the 3-position have also been described. The desacetylcephalosporins have a 3-hydroxymethyl substituent. The 3-alkylthiomethyl and 3-heteroarylthiomethyl cephalosporins have also been described. More recently, certain 3-methoxymethylcephalosporins were disclosed in U.S. Pat. No. 3,665,003 and 3-bromomethylcephalosporins were disclosed in U.S. Pat. Nos. 3,647,788, 3,668,203 and 3,637,678.
In addition to the 3-methyl or 3-substituted methyl cephalosporins, 3-formyl substituted cephalosporins have also been disclosed. In U.S. Pat. No. 3,351,596, issued Nov. 7, 1967, Chamberlin claimed a process comprising reacting a 3-hydroxymethyl-7-acylamino-3-cephem-4-carboxylic acid compound with a diazo compound to obtain a 3-formylcephalosporin ester and then reacting that ester with an oxidizing agent selected from the group consisting of manganese dioxide and chromium trioxide. A similar conversion was described in Belgium Pat. No. 768,653. The corresponding 3-formylcephalosporin sulfoxides were disclosed in U.S. Pat. No. 3,674,784.
Another class of cephalosporins differing in the nature of the substituent at the 3-position was described in Netherlands Pat. No. 7,206,931, wherein certain 3-unsubstituted cephalosporins, as well as a method for their preparation by decarbonylation of the corresponding 4-formyl compounds.
It is an object of this invention to provide new cephalosporin compounds which are useful as antibiotics or as intermediates in processes for preparing antibiotics.
It is another but more specific object of this invention to provide new structurally unique compounds of the cephalosporin class, wherein a carboxy group or a derivative thereof is attached directly to the carbon in the 3-position of the dihydrothiazine ring.